In the past, orally-disintegrating tablets have been developed in highly convenient forms which can safely be taken by patients who have difficulty in swallowing drugs, elderly people, children, etc. and which can easily be taken without water. It is important that orally-disintegrating tablets have sufficient breaking strength (tablet hardness) such that any cracks, powdering, etc. are not caused in the tablets during production or transportation of the tablets or during breaking the seals in the same manner as general tablets, and also, it is important that orally-disintegrating tablets have excellent disintegrability (disintegration time) such that the tablets immediately disintegrate in the oral cavity.
The tablet hardness and disintegrability are mutually opposing properties. In general, when a molding pressure is increased to increase the hardness, the disintegration time tends to be prolonged, and, when the molding pressure is reduced to shorten the disintegration time, the hardness tends to be smaller. Therefore, various technologies have been developed in order to cope with both the two properties or to achieve an optimal balance between the two properties.
Furthermore, components of the particles, granulation methods, etc. have been studied in order to impart superior moldability to particles or particulate compositions constituting tablets.
The present inventors have already developed a method of producing a disintegrative particulate composition having an excellent disintegrability and tablet hardness, or having a higher tablet hardness without substantially extending disintegration time (Patent Literature (PTL) 1).
Furthermore, it has been developed a disintegrative particulate composition comprising the four components consisting of a first disintegrator component of an acid-type carboxymethylcellulose, a second disintegrator component other than the acid-type carboxymethylcellulose, an excipient of a sugar or sugar alcohol, and crystalline cellulose (PTL 2).
Furthermore, cellulose that is produced from a vegetable fiber and having a fiber diameter (a short diameter) or thickness of from about a few m to several hundreds nm has been generally known as “fine-fibrillated cellulose” or “micro-fibrillated cellulose.” The production examples and its structure, properties and functions are described in PTL 5 and PTL 6 cited below.
In the fine- or micro-fibrillated cellulose, a surface area has been increased, hydrophilic property that is the original characteristics of cellulose has been significantly strengthened, and a three-dimensional network has been formed, without deteriorating basic properties such as physical and chemical stabilities of a starting material of cellulose. As a result, when it is formulated into goods in a paste or cream shape, it will show a water-retaining (syneresis-preventing) property and a form-retaining property due to the interaction with water and oil droplets, fine particles, etc. It is also utilized to modify goods in a jelly form, for example, to increase their strength.
Accordingly, the above cellulose has been widely used in various applications, for example, as a binder for powder and fibrous materials, a paper strong agent in papermaking, a thickening agent for improving food texture of foods, a humectant for water-retaining of foods, a filter aid for alcoholic beverage and the like.
As an application example of the micro-fibrillated cellulose, PTL 7 describes a gelly composition comprising a water-dispersible complex comprising the micro-fibrillated cellulose and a hydrophilic polymer that is soluble in warm water in a particular ratio; a gelling agent; and water in a particular ratio. It describes that the composition has properties to inhibit denaturation of proteins and precipitation of water-insoluble components during heating or warming treatment and to give a good food texture.
PTL 8 describes a gelling agent comprising a highly dispersible cellulose complex comprising the micro-fibrillated cellulose, a water-soluble polymer and hydrophilic substance in a particular ratio; and a particular kind of polysaccharide in a particular ratio. It describes that the agent is characterized as being superior in disintegration and dispersion in water when compared to a conventional highly dispersible cellulose complex, so that it can be used in industrial and practical dispersing conditions.
Thus, the micro-fibrillated cellulose is used as a one component in the gelly composition and gelling agent disclosed in PTL 7 and 8. Furthermore, the hydrophilic polymer is an essential component for the water-dispersible complex of PTL 7, and the water-soluble polymer is an essential component for the highly dispersible cellulose complex of PTL 8.
PTLs 3 and 4 disclose an orally-disintegrative particulate composition and an orally-disintegrating tablet, which comprise lactose. They are said to have an excellent disintegrability and practically sufficient hardness.
However, as described in an example of PTL 3, an orally-disintegrating tablet actually produced has hardness in a range of 40 and 60 N and oral disintegration time of dozens of seconds, which are not higher or faster than those of the other arts. Also, as described in an example of PTL 4, the hardness of an orally-disintegrating tablet produced using granulated lactose is 3.7 kgf (36N), which is not so high, either.